The role of endogenous nitric oxide in the sympathetic and hemodynamic response to platelet activating factor-induced hypotension in anesthetized dogs.
We previously demonstrated that platelet-activating factor (PAF) when injected intravenously decreases renal sympathetic nerve activity in anesthetized dogs. Recently, nitric oxide (NO) has been shown to inhibit renal sympathetic nerve activity. The present study was designed to determine, using the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), whether endogenous NO contributes to the PAF-induced renal sympatho-inhibition in anesthetized dogs. We also determined the role of NO in systemic and pulmonary hemodynamics during PAF-induced hypotension. In response to PAF (10 microg x kg(-1), intravenously), renal sympathetic nerve activity showed similar responses in animals pretreated with L-NAME (n = 7; 20 mg x kg(-1) bolus and .05 mg x kg(-1) x min[-1]), D-NAME (n = 7), and phenylephrine (n = 7), as characterized by an initial increase (230%) followed by a decrease (56%). The depressor response to PAF was also similar as early as 10 min after injection in all PAF-injected groups. In contrast, L-NAME pretreatment potentiated PAF-induced pulmonary hypertension. Pulmonary arterial pressure 10 min after PAF in the L-NAME group (25+/-2 mmHg) was significantly greater than that in the D-NAME group (12+/-3 mmHg). In conclusion, endogenously produced NO is not involved in PAF-induced renal sympathetic nerve response or hypotension but attenuates PAF-induced pulmonary hypertension at the early stage in anesthetized dogs.
Wang
H G
HG
Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
Shibamoto
T
T
Matsuda
Y
Y
Koyama
S
S
D000777:Anesthetics; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects*; D006976:Hypertension, Pulmonary / Q000139:chemically induced; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010972:Platelet Activating Factor / Q000633:toxicity*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014666:Vasomotor System / Q000187:drug effects
D000777:Anesthetics; D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester